The present invention relates to a method for selecting pipetting parameters for a liquid, in which a fluid chamber is connected to a measuring chamber and the internal pressure of this measuring chamber is monitored using a pressure transducer, and in which at least a first part of this fluid chamber is brought into fluid connection with a sample of this liquid. Especially preferred embodiments of the method according to the present invention relate to a pipetting device for liquid handling of liquid samples.
The present invention thus comprises a method for selecting pipetting parameters for liquids in a pipetting device for aspirating and dispensing liquid volumes, such as samples, of human bodily fluids. Such a pipetting device comprises a pipette tip which is connected to a pump.
Industrial branches which are concerned, for example, with pharmaceutical research or clinical diagnostics using biochemical technologies require facilities for processing liquid volumes and liquid samples. Automated facilities typically comprise a single pipetting device or multiple pipetting devices which are used on liquid containers located on the worktable of a workstation. Such workstations are often capable of executing greatly varying work on these liquid samples, such as optical measurements, pipetting, washing, centrifuging, incubation, and filtration. One or more robots, which operate according to Cartesian or polar coordinates, may be used for sample processing at such a workstation. Such robots may carry and relocate liquid containers, such as sample tubes or microplates. Such robots may also be used as “robotic sample processors” (RSP), such as a pipetting device for aspirating and dispensing, or as a dispenser for distributing liquid samples. Preferably, such facilities are monitored and controlled by a computer. A decisive advantage of such facilities is that large numbers of liquid samples may be processed automatically over long time spans of hours and days without a human operator having to engage in the processing process.
Pipetting devices known from the prior art (cf., for example, U.S. Pat. No. 4,675,301, U.S. Pat. No. 4,794,085, and U.S. Pat. No. 5,723,795) comprise a pipette tip which is connected to a pump. Some of these devices comprise a fluid chamber, to which a pressure transducer having a pressure sensor is connected via a gas-filled chamber. This fluid chamber is defined by the pipette tip, a first line which connects the pipette tip to a pump, and an active part of this pump.
When pipetting liquids, the question of their type often arises, i.e., the physical features or constants of this liquid. Classifying liquids on the basis of their physical constants, such as surface tension, viscosity, or vapor pressure, is therefore known from the prior art. The suitable pipetting parameters may then be determined on the basis of the corresponding classification and these liquids may be pipetted with improved precision.
Measuring the viscosity of a liquid sample using a pipetting device is known from EP 0 608 425. In this case, one proceeds from a time span which is required to change a defined, original partial vacuum applied via a pipette tip used for aspirating the liquid by a specific amount. This time value is compared to known viscosity data related to such time values in a table and the current viscosity of the liquid is thus ascertained. When this method is applied, with centrifuged blood samples, the remaining fraction having the red blood cells may be collected separately from the blood plasma.
However, as explained above, other parameters also play a significant role in pipetting. Thus, because of the differing vapor pressures, it is known that samples of water or acetone must be pipetted in completely different ways. The surface tension of these solvents also differs greatly. The viscosity, the vapor pressure, and the surface tension are specified for several typical solvents in Table 1 as an illustration.
TABLE 1SolventViscosityVapor pressureSurface tension(at 20° C.)[mPas][hPa][mN/m]Water1.0022372.8DMSO2.140.5643.0Acetone0.3224023.3Ethanol1.25922.3
It is obvious from Table 1 that the surface tensions of acetone and ethanol are very similar. Nonetheless, these two solvents are not to be treated identically during pipetting because of the very different values of their parameters of viscosity and/or vapor pressure. It is thus obvious that it hardly suffices to determine only one parameter in order to be able to automatically and reliably pipette such different solvents, which are used routinely in all biochemical laboratories. Detecting all of these parameters (and possibly even further parameters such as the wettability of the pipette tip as a function of the liquid to be pipetted and/or the material used for the pipette tip) would require too much machine and time outlay, however. This is true above all when, in case of an automated workstation, the throughput of hundreds or thousands of samples within the shortest possible time must be ensured. This is certainly made more difficult if the solvents and/or liquid samples are unknown compositions having unknown physical parameters, which must also be pipetted automatically as much as possible.